{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:11:02Z","timestamp":1779340262462,"version":"3.51.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a degenerative joint disease with complex molecular mechanisms. There is an interplay between programmed cell death (PCD) and extracellular matrix (ECM) in inflammatory diseases. This study aimed to identify a key PCD\/ECM-related gene involved in OA pathogenesis through multi-omics analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      RNA-seq data of OA synovial tissue from the GEO databases were analyzed. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, cross analysis, and protein-protein interaction (PPI) network were used to identify key PCD\/ECM-related genes in OA. Regulatory networks were predicted using miRDB, TargetScan, and miRWalk databases, and transcription factor binding was analyzed using JASPAR and FIMO. The role of\n                      <jats:italic>MSR1<\/jats:italic>\n                      in OA progression was investigated by establishing an IL-1\u03b2-induced\n                      <jats:italic>in vitro<\/jats:italic>\n                      OA cell model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 517 genes associated with OA that were enriched in immune and developmental pathways. Differential expression analysis and cross-analysis revealed 24 OA-associated PCD- and ECM-related genes.\n                      <jats:italic>MSR1<\/jats:italic>\n                      was identified as the key candidate via PPI network analysis. In both the training and validation sets,\n                      <jats:italic>MSR1<\/jats:italic>\n                      expression was higher in OA samples than in healthy samples, with an AUC value greater than 0.7.\n                      <jats:italic>MSR1<\/jats:italic>\n                      expression was positively correlated with key immune populations and microenvironment scores, suggesting a role for\n                      <jats:italic>MSR1<\/jats:italic>\n                      in OA pathogenesis through immune modulation. In addition, molecular docking identified hesperidin as a high-affinity MSR1-binding compound with favorable interaction stability.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments demonstrated that\n                      <jats:italic>MSR1<\/jats:italic>\n                      was upregulated in IL-1\u03b2\u2013induced OA-like chondrocytes and promoted apoptosis, extracellular matrix degradation, and NF-\u03baB pathway activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study highlights PCD\/ECM-related gene\n                      <jats:italic>MSR1<\/jats:italic>\n                      as a central regulator of OA pathogenesis and proposes hesperidin as a potential therapeutic agent. The integrative approach provides a framework for understanding OA mechanisms and drug discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1777038","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:45:36Z","timestamp":1779338736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative multi-omics identifies MSR1 as a programmed cell death and extracellular matrix hub gene in osteoarthritis with hesperidin targeting potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinquan","family":"Bao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia Autonomous, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated 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